Monitoring blood glucose levels in a diabetic individual is important for maintaining metabolic control in the individual. Currently-available systems and methods of monitoring glucose levels require extraction of blood from the diabetic individual at multiple times during each day, e.g., finger prick. As such, only information about blood glucose levels at discrete time points is made available. Additionally, extracting blood for use in testing can be painful, and as a result, can lead to low compliance or non-compliance by diabetic individuals.
Efforts have therefore been made to develop an effective system and method for monitoring blood glucose levels in a continuous and less invasive manner. Biosensors have been proposed for use in the in vivo, continuous detection of blood analyte levels. A biosensor includes an element capable of specifically detecting an analyte of interest, allowing a measurable signal to be produced, which can be correlated to analyte concentration.
Biosensors for detecting glucose can include an element that selectively binds glucose. For example, wild type glucose binding protein (wtGBP) is capable of binding glucose. GBP of Escherichia coli is a 33 kDa periplasmic binding protein. GBP consists of two distinctly similarly folded globular domains that are connected to each other by three peptide segments. The sugar binding site is located in the cleft of the protein formed between the two domains. The binding of glucose is accompanied by a conformational change of the protein at the hinge region. In the open form of GBP (in the absence of glucose) the two domains are far apart and the cleft is exposed to the solvent, while in the closed form the glucose is engulfed in the cleft.
Although biosensors have made use of certain wtGBPs, such biosensors have drawbacks. For example, GBPs are not very stable at room temperature. As such, there are apparent problems associated biosensors that make use of wtGBP for monitoring blood glucose levels in diabetic patients. Furthermore, currently-available systems and methods for continuously-detecting glucose are associated with a significant inability to detect glucose levels in the hypoglycemic ranges in a reliable manner. Further, these available systems also suffer from short lifespans and are not easily used for routine clinical use. In addition, the use of current wtGBPs for continuous blood glucose monitoring for implantable or catheter-based devices is complicated by the need for sterilization. The development of novel proteins with improved thermal and chemical stability will lead to easier and more cost-effective means of sterilization.
Accordingly, there is a need in the art for systems and methods for detecting glucose levels in a subject in a continuous manner, at ambient temperatures, with operability for clinical use, reliability, specificity, and sensitivity.